Description: The objectives of this core as described by the scientists are as follows: 1) design and exploitation of new molecular and cellular model systems for identifying and quantifying toxicity; 2) use of such systems for understanding uptake, metabolism, and regulation of the expression of toxicity; 3) design of mechanism-based measures to prevent and/or reverse toxicity; 4) development of scientific data of a type and form that will be useful for regulatory and environmental policy-making decisions. The faculty participating in this core all come from the Department of Molecular and Cellular Toxicology and include Drs. Armen Tashjian, Bruce Demple, Leona Samson, and Robert Schiestl. The current research activities are focused in genetic toxicology and cellular and biochemical toxicology. These research activities are supported by research grants (R0ls and P0ls) to each of the investigators above. The faculty also offer a Ph.D. training program in toxicology through the Program in Biological Sciences in Public Health at Harvard. Postdoctoral training occurs through participation in research in individual laboratories. There are currently 13 graduate students and 20 postdoctoral fellows in the Toxicology Program. Dr. Samson?s research is in the area of damage and repair of DNA and more specifically on the function and characteristics of DNA repair enzymes. Dr. Demple specializes in the area of oxidative stress, oxidative DNA damage, and enzymatic repair of oxidative DNA damage. Dr. Schiestl?s research is aimed at understanding the mechanism, genetic control, and inducibility of genome rearrangements such as deletions. His work is carried out mainly in yeast, but newer proposed efforts will shift to transgenic mice. Dr. Tashjian?s research is in the area of signal transduction, and the effect of chemical toxins on perturbation of signal transduction. The proposal describes in detailed, the past accomplishments and future plans for each of these investigators. This Scientific Core has had little participation in the past in the Center?s Facilities Cores, but it is claimed this will change in the new reorganization of the Center. Of the current faculty, only Dr. Schiestl seems to have participated recently in the Pilot Project program. The only collaborative interactions in this core and other programs in the Center seems to be between Drs. Schiestl and Brain.